Studies in the synthesis of o-glycosides

Abstract

Reaction of vinyl and substituted-vinyl glucosides ethenyl 2,3,4,6-tetra-O-acetyl-β-D-glucopyranoside, 1'-phenylethenyl 2,3,4,6-tetra-O-acetyl-β-D-glucopyranoside and 1'-{p-methoxyphenyl)ethenyl 2,3,4,6-tetra-O-acetyl-β-D-glucopyranoside with methanol in the presence of an extensive range of electrophiles afforded 2,3,4,6-tetra-O-acetyl-D-glucopyranose instead of the expected methyl 2,3,4,6-tetra-O-acetyl-D-glucopyranoside. The above glucosides are therefore found to be unsuitable glycosylating agents for methyl 2,3,4,6-tetra-O-acetyl-D-glucopyranoside synthesis. The unsaturated sugar derivative 3,4,6-tri-O-acetyl-D-glucal underwent glycosidation with ethanol in the presence of several Lewis acid and neutral catalysts to form ethyl 4,6-di-O-acetyl-2,3-dideoxy-D-erythro-hex-2-enopyranosides in good yields. Of these catalysts the great majority led to the formation of these glycosides in the α/β ratio (6±1):1. However, titanium(IV) chloride gave the α-anomer as the only glycosidic product. In all cases (E)-4,6-di-O-acetyl-2,3-dideoxy-aldehydo-D-erythro-hex-2-enose was formed as a by-product in about 12% yield. With this catalyst the sugar alcohol 1,2:3,4-di-O-isopropylidene-α-D-galactopyranose (diacetone galactose) afforded only 6-O-(4,6-di-O-acetyl-2,3-dideoxy-α-D-erythro-hex-2-enopyranosyl)-1,2:3,4-di-O-isopropylidene-α-D-galactopyranose (71% isolated) together with the above enal by-product. The titanium(IV) chloride-catalysed reaction of tri-O-acetyl-D-glucal with ethanol and diacetone galactose therefore improves the stereoselectivity and yield of the α-glycosidic products, but this effect was not found to be general.